Heavy metal poisoning is a serious medical problem which has received even more emphasis in recent years since toxic heavy metals such as lead and mercury may very easily enter the body as a consequency of accidents or environmental pollution. Of even more concern are radioactive toxic heavy metals which pose an additional problem due to their radioactivity. The ionizing radiations of the radioactive metals are of even greater concern than their chemical toxicity because of the risk of tumor induction from the radioactive ionization. Toxic heavy metals are known to concentrate in various organs of the body. Plutonium, for example, usually deposits in the liver, it being known that as much as 30 to 60% of an administered amount of plutonium will deposit in the liver. The toxic heavy metal, plutonium in this example, remains in the organ and is only very slowly removed, thereby increasing the potential for tumors.
In th past, the polyaminopolycarboxylic acid, ethylenediaminetetraacetic acid (EDTA) has been used as a chelating agent for removing toxic metals from animal tissues. More recently, a related polyaminopolycarboxylic acid, diethylenetriaminepentaacetic acid (DTPA) has been shown to have a greater ability to remove various heavy metals. The use of chelating agents for the removal of toxic heavy metals is based on their ability to form stable, nonionic, soluble and readily excretable complexes with the metal molecules in the tissues. They have proven valuable because they, in themselves, have a very low toxicity, are able to form soluble, excretable metal chelates within a body, and resist degradation by cell metabolites. However, a serious limitation for the use of chelating agents is that they exist as hydrated anions in the blood plasma. These anions are unable to penetrate cellular membranes. Therefore only extracellularly deposited toxic metals can be complexed by the chelating agents and removed from the body, whereas intracellularly deposited metals are not complexed by the chelating agent and therefore are not readily removed. Attempts have been made in the past to increase the penetration of chelating agents through cellular membranes such as by the esterification of polyaminopolycarboxylic acids, but these efforts have met with limited success because of the insolubility and toxicity of the esterified compounds.
It is an object of the present invention to provide a method for transferring a chelating agent across a cellular membrane.
Another object of the present invention is to provide a means for introducing a chelating agent into the interior of a cell.
It is another object of the present invention to provide a method for introducing a chelating agent into the interior of a cell of a living organism by introducing the chelating agent to the organism and carrying it to the cell in the blood stream.
Another object of the present invention is to provide a method for the removal of intracellularly deposited toxic heavy metals.
Still another object of the present invention is to provide a therapy method for toxic heavy metal poisoning whereby both intracellularly deposited toxic heavy metals as well as extracellularly deposited toxic heavy metals can be removed from the body.